THURSDAY, April 30 (HealthDay News) -- Two new studies provide more evidence that drugs such as Procrit and Aranesp, often used by cancer patients to fight anemia-linked fatigue, may boost the risk of death and serious adverse events such as blood clots.

These drugs, called erythropoiesis-stimulating agents (ESAs), have also been associated in prior studies with increased risk of heart attack, stroke and tumor growth. The primary argument for the continued use of these drugs is that they help reduce the number of blood transfusions some cancer patients need, while improving quality of life.

However, a co-author of one paper, Dr. Anthony Reiman, from the University of Alberta, Canada, said his team is "supporting other groups that are recommending great caution in using these drugs for cancer patients, and in routine circumstances they may not be indicated. We hope the drugs would still be made available for people for whom transfusion isn't a good option -- but those are very limited circumstances."

ESAs include erythropoietin (Epogen, Procrit) and darbepoetin (Aranesp). They work by stimulating the bone marrow to produce new red blood cells, according to the U.S. National Institutes of Health. They are used to treat anemia caused by chemotherapy and to treat anemia in people with chronic kidney disease who are on dialysis.

But rising concern led the U.S. Food and Drug Administration in 2007 to ask the drugs' manufacturers to add a "black box" warning to the medications. The warning indicates that the medications should be used at the lowest possible doses to avoid risks such as blood clots, heart attacks, stroke, congestive heart failure, increased tumor growth and an increased risk of death. The FDA also recommended that the medications be prescribed at the lowest doses possible because trials generally indicated an increased risk when blood levels were raised above 12 grams per deciliter.

The two new studies may buttress that move. In the first study, Reiman and other researchers analyzed data from 52 clinical trials that included more than 12,000 people.

The result: "The use of drugs to encourage red blood cell formation in cancer patients with anemia increases the risk of death and serious adverse events such as blood clots," according to co-researcher Dr. Scott Klarenbach, an assistant professor at the University of Alberta.

Although risk of death was only 15 percent to 16 percent higher among patients who used the drugs than those who did not, the high death rates among cancer patients means this increase could affect a significant number of people, the researchers say.

"These medications should not routinely be used as an alternative to blood transfusions in patients with anemia related to cancer, unless future studies demonstrate safety and clinical benefits," Klarenbach said. "While use of medications [instead of blood transfusion] may be appealing to both patients and practitioners, their use is associated with an increased risk of death."

"At best, these drugs don't seem to improve longevity," Reiman said. "They may have some benefits in improving quality of life."

The report is published in the April 30 online edition of the Canadian Medical Association Journal.

In another report, in the May 2 issue of The Lancet, researchers led by Dr. Julia Bohlius, from the University of Bern in Switzerland, looked at the findings from 53 cancer trials that included a total of almost 14,000 patients. More than 1,500 patients died during the study period, and almost 5,000 patients died overall.

The researchers found that ESAs were associated with a 17 percent increase in deaths during the study period. Among patients receiving chemotherapy, ESAs increased the death risk by 10 percent, they report.

The findings "show that erythropoiesis-stimulating agents increase mortality in all patients with cancer, and a similar increase might exist in patients on chemotherapy," the authors wrote. "In clinical practice, the increased risks of death and thromboembolic events should be balanced against the benefits of treatment with erythropoiesis-stimulating agents, taking into account each patient's clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumor progression, and meta-analyses similar to this one will address these questions," they added.

Dr. Charles Bennett, the A.C. Beuhler professor of geriatric medicine at the Feinberg School of Medicine at Northwestern University, helped conduct a study, published in the Journal of the American Medical Association early last year, that also found similar risks for the use of ESAs by cancer patients. He believes the new data support those findings.

"The message is clear: There is a safety concern that's real and significant," Bennett said.

In addition, Bennett believes that quality-of-life issues and the need for a reduction in blood transfusions for cancer patients are overstated. "The [appropriate] use of these drugs in the United States is for palliative care in cancer patients and I support that," he said.